The AMPK-mTOR Pathway Is Inhibited by Chaihu Shugan Powder, Which Relieves Nonalcoholic Steatohepatitis by Suppressing Autophagic Ferroptosis.

IF 4.4 3区 医学 Q2 CELL BIOLOGY
Mediators of Inflammation Pub Date : 2024-10-28 eCollection Date: 2024-01-01 DOI:10.1155/2024/4777789
Zheng Liang, Dajin Pi, Jianwei Zhen, Haizhen Yan, Chuiyang Zheng, July Liang Chen, Wen Fan, Qingliang Song, Jinyue Pan, Dongdong Liu, Maoxing Pan, Qinhe Yang, Yupei Zhang
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Abstract

Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine-choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR)-mediated autophagy and ferroptosis markers, such as p-AMPKα/AMPKα, p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH.

柴胡舒筋粉抑制AMPK-mTOR通路,通过抑制自噬铁蛋白沉积缓解非酒精性脂肪性肝炎
非酒精性脂肪性肝炎(NASH)是非酒精性脂肪肝(NAFLD)的晚期阶段,主要表现为肝脏脂肪堆积、肝细胞受损和炎症。柴胡舒肝散(CSP)是一种著名的中药复方制剂,在中国被广泛用于治疗肝病,其在减少脂质堆积和有效抗炎方面的功效已得到证实。因此,本研究的主要目的是通过评估肝脏组织病理学、脂质组分析和基因表达,研究 CSP 对 NASH 的影响和可能机制。为了诱导小鼠建立 NASH 模型,我们采用了一种缺乏蛋氨酸和胆碱的饮食,即蛋氨酸胆碱缺乏(MCD)饮食。最初,我们通过评估血清和肝脏指标的水平来研究给 NASH 小鼠服用 CSP 的影响。我们发现,CSP 能够减少小鼠体内的脂质堆积和炎症。此外,共有 1009 个基因在自噬和铁突变通路中表现出富集。单磷酸腺苷激活的蛋白激酶-雷帕霉素哺乳动物靶标(AMPK-mTOR)介导的自噬和铁突变标志物,如p-AMPKα/AMPKα、p-mTOR/mTOR、Beclin-1、微管相关蛋白1轻链3γ(LC3)、p62(sequestosome 1)和p62(sequestosome 1)的肝脏蛋白水平均有所提高、p62(序列组 1 [SQSTM1/p62])、Kelch 样 ECH 相关蛋白 1 (KEAP1)、核因子红细胞 2 相关因子 2 (Nrf-2)、铁蛋白重链 1 (FTH1) 和谷胱甘肽过氧化物酶 4 (GPX4)在 CSP 的作用下得到恢复。此外,我们的研究结果表明,抑制自噬对小鼠模型中铁蛋白沉着症的发生有抑制作用,这表明自噬激活可能在介导NASH中的铁蛋白沉着症中发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Mediators of Inflammation
Mediators of Inflammation 医学-免疫学
CiteScore
8.70
自引率
0.00%
发文量
202
审稿时长
4 months
期刊介绍: Mediators of Inflammation is a peer-reviewed, Open Access journal that publishes original research and review articles on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules.
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